Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients.
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PMID:Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus. 1574 4

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.
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PMID:Can brain dysfunction be a predisposing factor for metabolic syndrome? 1575 41

The metabolic syndrome is a cluster of metabolic and vascular abnormalities that include central obesity, insulin resistance, hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk of coronary and cerebral vascular disease. These metabolic and vascular abnormalities are the main cause of cardiovascular mortality in western societies. Endothelial dysfunction, an early step in the development of atherosclerosis, has been reported in obese nondiabetic individuals and in patients with Type 2 diabetes. It has also been observed in individuals at high risk for Type 2 diabetes, including those with impaired glucose tolerance and the normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence points to adipocytes as a complex and active endocrine tissue whose secretory products, including free fatty acids and several cytokines (i.e., leptin, adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a major role in the regulation of human metabolic and vascular biology. These adipocytokines have been claimed to be the missing link between insulin resistance and cardiovascular disease. Interventions designed to improve endothelial and/or adipose-tissue functions may reduce cardiovascular events in obese individuals with either the metabolic syndrome or Type 2 diabetes. Lifestyle modification in the form of caloric restriction and increased physical activity are the most common modalities used for treating those individuals at risk and is unanimously agreed to be the initial step in managing Type 2 diabetes. Several recent studies have demonstrated favorable impacts of lifestyle modifications in improving endothelial function and insulin sensitivity, in addition to altering serum levels of adipocytokines and possibly reducing cardiovascular events. This review discusses current knowledge of the role of lifestyle modifications in ameliorating cardiovascular risk in obese subjects with either the metabolic syndrome or Type 2 diabetes.
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PMID:Lifestyle modification and endothelial function in obese subjects. 1585 97

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.
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PMID:The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology. 1585 36

Atherosclerotic CVD is the most common cause of death in the West. Yet, its pathogenesis and early development are only partially understood. Central to the early atherosclerotic process is impairment of vascular endothelial function. Endothelial dysfunction can be measured non-invasively and is evident in children before clinical manifestations of atherosclerosis in adulthood. Factors in early life, such as conventional cardiovascular risk factors, or programming by perinatal growth and nutrition strongly affect endothelial function and hence the development of atherosclerosis and CVD. For instance, low birth weight and faster growth early in infancy have a detrimental effect on vascular structure and function. Childhood obesity, a key independent risk factor for CVD, also adversely affects early vascular health. Obesity is associated with endothelial dysfunction and greater arterial stiffness from as early as the first decade of life, while weight loss is beneficial. This effect on vascular function is probably mediated in part by low-grade inflammation and insulin resistance associated with obesity or by the production by adipose tissue of cytokine-like molecules, collectively termed adipokines. A high leptin concentration, in particular, is found in obese individuals and is strongly associated with vascular changes related to early atherosclerosis. The present review focuses on the early origins of endothelial dysfunction, emphasising the role of obesity. It also considers the mechanisms by which obesity impairs endothelial function, understanding of which will be important to further scientific knowledge and to improve public health.
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PMID:Endothelial dysfunction: role in obesity-related disorders and the early origins of CVD. 1587 18

Adipose tissue has recently emerged as an active endocrine organ that secretes a variety of metabolically important substances, collectively called adipocytokines or adipokines. In this review we summarize the effects of the adipokines leptin, adiponectin, and resistin on the vasculature and their potential role for pathogenesis of vascular disease. Leptin is associated with arterial wall thickness, decreased vessel distensibility, and elevated C reactive protein (CRP) levels. Leptin possesses procoagulant and antifibrinolytic properties, and it promotes thrombus and atheroma formation, probably through the leptin receptors by promoting vascular inflammation, proliferation, and calcification, and by increasing oxidative stress. Research for development of pharmacologic antagonism for the leptin receptor is currently under way. Adiponectin inhibits the expression of the adhesion molecules ICAM-1, VCAM-1, and P selectin. Therefore, it interferes with monocyte adherence to endothelial cells and their subsequent migration to the subendothelial space, one of the initial events in the development of atherosclerosis. Adiponectin also inhibits the transformation of macrophages to foam cells in vitro and decreases their phagocytic activity. Resistin, discovered in 2001, represents the newest of the adipokines and was named for its ability to promote insulin resistance. Resistin increases the expression of the adhesion molecules VCAM-1 and ICAM-1, up-regulates the monocyte chemoattractant chemokine-1, and promotes endothelial cell activation via ET-1 release. Although many aspects of its function need further clarification, it appears that resistin will add significantly to our knowledge of the pathophysiology of vascular disease and the metabolic syndrome.
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PMID:Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease. 1591 85

Circulating endothelial progenitor cells (EPCs) may be involved in the maintenance of vascular homeostasis and their impairment may be conducive to vascular disease. We studied the role of an adipocyte-derived hormone, leptin, in the regulation of human EPC function. EPCs were grown from human circulating mononuclear cells. The presence of the leptin receptor and the functional effects of leptin in EPCs were investigated. EPCs stained positive for endothelial cell markers (Flk-1 and Tie-2 receptors) and the hematopoietic CD34 marker. The presence of the long form of the leptin receptor in EPCs was confirmed by Western blotting and with immunofluorescence. Leptin, at a physiological concentration of 10 ng/ml, significantly increased tube formation from 2.1+/-2.2 to 12.4+/-4.9 tubes/25 mm2. At a higher concentration of 100 ng/ml of leptin, tube formation was reduced compared to the lower concentration. This higher concentration of leptin also inhibited EPC migration, decreasing it from 0.45+/-0.14 to 0.28+/-0.12 mm/48 h. Leptin did not have any effect on EPC proliferation. In summary, the leptin receptor is present in human EPCs and leptin may affect EPC function, both in physiological and in hyperleptinemic conditions. These findings are relevant to leptin-mediated regulation of vasculogenesis in humans, and the association between hyperleptinemia and obesity with cardiovascular disease.
Atherosclerosis 2005 Nov
PMID:Leptin receptor and functional effects of leptin in human endothelial progenitor cells. 1595 Sep 78

Understanding the risk and pathogenesis of the numerous disorders including the insulin resistance/metabolic syndrome has changed meaningfully in the recent years. The remarkable similarity of the risk factors of cardiovascular disease, type 2 diabetes mellitus, obesity and atherogenic dyslipidemia induced to search for their pathophysiology. The aim of these examinations was to determine if the inflammatory state is a soil of the metabolic syndrome as in atherosclerosis? Increasing number of studies demonstrates a series of statistically significant correlations between the inflammatory markers and diseases present in the metabolic syndrome. It allows for the reasonable basis of hypothesis that chronic, mild inflammatory state underlies not only the cardiovascular disease, but also is the soil of the metabolic syndrome pathologies and its complications development. Both associations between the inflammatory mediators as CRP, fibrinogen, alpha1-glycoproteins, leptin, TNFalpha, PAI-1 and the metabolic syndrome variables, chiefly obesity, seem to suggest that both atherosclerosis and insulin resistance are the results of chronic activation of the nonspecific (innate) immune system. According to this hypothesis, daily stresses as traumas, infections and emotions would lead to primary immune and neuroendocrine systems alterations. By this manner, whole body metabolic disorders and metabolic syndrome component progressive reveal would approach. In this context, metabolic syndrome might be defined as an immunemetabolic disease.
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PMID:[Metabolic or immunometabolic syndrome?]. 1599 65

Leptin is an adipocyte-derived hormone that plays a major role in the regulation of energy homeostasis through its action in the central nervous system. Leptin also acts on several peripheral tissues, including the vascular endothelium. The leptin receptor has been identified in endothelial cells. Leptin action on the endothelium modulates several physiologic processes, with potential implications in pathophysiologic diseases associated with obesity. Leptin stimulation of angiogenesis has attracted attention because of its potential involvement in retinopathy and atherosclerosis. Leptin activation of endothelial oxidative stress also has implications in atherosclerosis and inflammation. However, data on the impact of the endothelial effect of leptin on arterial pressure are contrasting. Although some investigators have shown that leptin action on the endothelial nitric oxide system tends to decrease arterial pressure, others have shown no contribution from the endothelial effect of leptin to the control of arterial pressure. Further characterization of the endothelial effects of leptin will, it is hoped, help in the understanding of the different pathophysiologic diseases associated with obesity.
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PMID:Endothelial effects of leptin: implications in health and diseases. 1603 75

Adipose tissue, in addition to the storage of lipids function for lipids, plays active roles in normal metabolic homeostasis and in the development of several diseases, such as type 2 diabetes, dyslipaemia and atherosclerosis. These roles are mediated by adipocytokines, factors secreted by adipose tissue. These include tumor necrosis factors (TNF)-alpha, leptin, resistin, adiponectin or visfatin. Adipocytokines act in an autocrine, paracrine and endocrine manner. Adiponectin is a peculiar adipocytokine because in contrast to the markedly increased levels of leptin, resistin or TNF-alpha in obesity, its level is negatively correlated with body mass index, and is decreased in presence of insulin resistance and in type 2 diabetes. Adiponectin may play a crucial role in the development of diabetes mellitus and high adiponectin levels should protect against impairment of glucose metabolism. Moreover, adipocytokines are involved in the pathogenesis of vascular diseases and may represent a link between obesity, diabetes, inflammation and atherosclerosis. Weight loss, exercise and some antidiabetic drugs also influence plasma adipocytokines levels. For instance, thiazolidinediones treatment in patients with type 2 diabetes resulted in an increased in plasma adiponectin levels and a decrease in circulating TNF-alpha concentrations.
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PMID:[Adipocytokines: link between obesity, type 2 diabetes and atherosclerosis]. 1603 96


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